Prenatal diagnosis of Roberts syndrome and detection of an ESCO2 frameshift mutation in a Pakistani family

Abstract

We report two siblings with Roberts syndrome (RBS), and an attempt to delineate the underlying molecular mechanism leading to familial recurrence. Cytogenetic studies and direct sequencing of the ESCO2 gene were carried out in the second affected fetus and the parents. Fetal DNA was obtained from amniocytes after amniocentesis. Parental DNA was obtained from peripheral blood samples. Cytogenetic analysis of amniocytes revealed a normal male karyotype in 20 analyzed metaphases and chromosomal aneuploidies in 10 metaphases. All metaphases displayed premature separation of centromeres and puffing of heterochromatic regions near the centromere. A homozygous mutation leading to a frameshift in ESCO2 was identified in the fetal DNA sample. Both parents are heterozygous carriers of the same mutation. The present case demonstrates the prenatal diagnosis of RBS associated with a frameshift mutation in ESCO2.